Package leaflet: Information for the user

Xanirva, 15 mg, film-coated tablets
Xanirva, 20 mg, film-coated tablets
Rivaroxabanum
Read the entire leaflet before taking this medicine because it contains important information
for the patient.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any adverse reactions, including any possible side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents:

What Xanirva is and what it is used for
Important information before taking Xanirva
How to take Xanirva
Possible side effects
How to store Xanirva
Contents of the pack and other information

1. What Xanirva is and what it is used for

Xanirva contains the active substance rivaroxaban and is used in adults to:

prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body in patients who have a type of irregular heartbeat called non-valvular atrial fibrillation.
treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent recurrence of blood clots in the veins and/or lungs. Xanirva is used in children and adolescents under 18 years of age and with body weight of 30 kg or more to:
treat blood clots and prevent recurrence of blood clots in the veins or in the blood vessels of the lungs, after at least 5 days of initial treatment with injectable medicines used to treat blood clots.

Xanirva belongs to a group of medicines called anticoagulants. It works by
blocking a blood clotting factor (factor Xa), thereby reducing the tendency to form
blood clots.

2. Important information before taking Xanirva

When not to take Xanirva:

if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6);
if the patient has excessive bleeding;
if the patient has a disease or condition of an organ that leads to an increased risk of serious bleeding (e.g. stomach ulcer, trauma or bleeding into the brain, recent surgery on the brain or eyes);
if the patient is taking other medicines that prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain the patency of a catheter in a vein or artery;
if the patient has a liver disease that leads to an increased risk of bleeding;
if the patient is pregnant or breastfeeding.

Do not use Xanirva and inform your doctor if you suspect that any of the above circumstances apply to you.
Warnings and precautions
Talk to your doctor or pharmacist before taking Xanirva.
When to exercise special caution with Xanirva

if the patient has an increased risk of bleeding, such as in the following conditions:
- severe kidney disease in adults and moderate or severe kidney disease in children and adolescents, as kidney function may affect the amount of medicine acting in the patient's body;
- taking other medicines that prevent blood clots (e.g. warfarin, etexilate dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain the patency of a catheter in a vein or artery (see section "Other medicines and Xanirva");
- bleeding disorders;
- very high blood pressure that does not decrease despite medication;
- stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestines and stomach or inflammation of the oesophagus (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus) or tumours located in the stomach or intestines or in the genital or urinary system;
- blood vessel disease in the back of the eye (retinopathy);
- lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous bleeding from the lungs;
in patients with prosthetic heart valves;
in patients with antiphospholipid syndrome (immune system disorders that increase the risk of blood clots). Inform your doctor, who will decide whether to change the treatment if necessary;
if the patient has been diagnosed with abnormal blood pressure or is scheduled for surgery or other treatment to remove a blood clot from the lungs.

If you suspect that any of the above applies to you, inform your doctor before taking Xanirva. Your doctor will decide whether to use this medicine and whether you require particularly close monitoring.
If you are going to have surgery:

it is very important to take Xanirva exactly at the times prescribed by your doctor, both before and after surgery;
if catheterisation or lumbar puncture of the spine is planned during surgery (e.g. for epidural or spinal anaesthesia or for pain relief):
- it is very important to take Xanirva exactly at the times prescribed by your doctor, both before and after the puncture or removal of the catheter;
contact your doctor immediately if, after the anaesthesia ends, you experience numbness or weakness in the legs, or disturbances in bowel or bladder function, as immediate treatment may be required.

Children and adolescents
Xanirva 15 mg tablets are not recommended for children weighing less than 30 kg.
Xanirva 20 mg tablets are not recommended for children weighing less than 50 kg.
There is insufficient data on the use of rivaroxaban in children and adolescents for indications approved in adults.
Xanirva and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription.

If you are taking:
- certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only topically on the skin;
- ketoconazole tablets (used in the treatment of Cushing's syndrome, in which the body produces too much cortisol);
- certain antibiotics (e.g. clarithromycin, erythromycin);
- certain antiviral medicines used in HIV infection or AIDS treatment (e.g. ritonavir);
- other medicines used to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin or acenocoumarol);
- anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid);
- dronedarone, a medicine used to treat heart rhythm disorders;
- certain medicines used to treat depression (selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)).

If you suspect that any of the above applies to you, inform your doctor before taking Xanirva, as the effect of Xanirva may be increased when taken together with the above-mentioned medicines. Your doctor will decide whether to use this medicine and whether you require particularly close monitoring.
If your doctor considers that you have an increased risk of developing stomach or duodenal ulcers, they may prescribe treatment to prevent peptic ulcer disease.

If you are taking:
- certain antiepileptic medicines (phenytoin, carbamazepine, phenobarbital);
- St John's wort ( Hypericum perforatum ), an herbal medicine used for depression;
- rifampicin, which belongs to the group of antibiotics.

If you suspect that any of the above applies to you, inform your doctor before taking Xanirva, as the effect of Xanirva may be reduced when taken together with the above-mentioned medicines. Your doctor will decide whether to use Xanirva and whether you require particularly close monitoring.
Pregnancy and breastfeeding
Do not use Xanirva if you are pregnant or breastfeeding. If there is a risk that you may become pregnant, you should use an effective method of contraception during treatment with Xanirva. If you become pregnant while taking Xanirva, inform your doctor immediately, who will decide on further treatment.
Driving and using machines
Xanirva may cause dizziness (common side effects) and fainting (uncommon side effects) (see section 4 "Possible side effects"). Patients experiencing these side effects should not drive, ride a bicycle, or operate tools or machinery.
Xanirva 15 mg and 20 mg contain monohydrate lactose (a type of sugar) and sodium
If you have previously been diagnosed with intolerance to certain sugars, you should consult your doctor before taking this medicine.
The medicine contains less than 1 mmol of sodium (23 mg) per tablet, which means it is essentially "sodium-free".

3. How to take Xanirva

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Xanirva should be taken with food. The tablet(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the whole tablet, discuss alternative methods of taking Xanirva with your doctor. The tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, the patient should promptly eat a meal.
If necessary, a doctor may administer crushed Xanirva tablets via a gastric tube.

How many tablets to take

Adults

For prevention of blood clots in the brain (stroke) and other blood vessels in the body
The recommended dose is one 20 mg Xanirva tablet once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg Xanirva tablet once daily. If the patient requires a procedure to open blocked blood vessels in the heart (called percutaneous coronary intervention - PCI with stent placement), there is limited evidence supporting dose reduction to one 15 mg Xanirva tablet once daily (or one 10 mg Xanirva tablet once daily in case of renal impairment), in combination with an antiplatelet medicine such as clopidogrel.
For treatment of blood clots in the veins of the legs, blood clots in the blood vessels of the lungs, and prevention of recurrence of blood clots
The recommended dose is one 15 mg Xanirva tablet twice daily for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one 20 mg Xanirva tablet once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one 10 mg tablet once daily or one 20 mg tablet once daily. If the patient has kidney problems and is taking one 20 mg Xanirva tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Xanirva tablet once daily if the risk of bleeding is greater than the risk of developing further blood clots.

Children and adolescents
The dose of Xanirva depends on body weight and will be calculated by the doctor.

The recommended dose for children and adolescents with body weight from 30 kg to below 50 kg is one 15 mg Xanirva tablet once daily.
The recommended dose for children and adolescents with body weight 50 kg or more is one 20 mg Xanirva tablet once daily.

Each dose of Xanirva should be taken with a meal, accompanied by a drink (e.g. water or juice). Tablets should be taken every day at approximately the same time. Consider setting an alarm as a reminder. For parents or caregivers: observe the child to ensure the full dose has been taken. Since the dose of Xanirva depends on body weight, it is important to attend scheduled doctor appointments, as dose adjustments may be necessary due to changes in weight. Never adjust the dose of Xanirva on your own. If needed, the doctor will adjust the dose.

Do not split the tablet to achieve a partial dose. If a lower dose is required, use another medicine containing rivaroxaban in the form of granules for oral suspension.
For children and adolescents who are unable to swallow whole tablets, use a medicine containing rivaroxaban in the form of granules for oral suspension.
If the oral suspension is not available, the Xanirva tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, the patient should eat a meal.
If necessary, the doctor may also administer crushed Xanirva tablets via a gastric tube.

If a dose is vomited or spat out

Within 30 minutes of taking Xanirva, take a new dose.
More than 30 minutes after taking Xanirva, do not take a new dose. In this case, take the next dose of Xanirva at the usual time.

Contact your doctor if vomiting or spitting out the dose occurs repeatedly after taking Xanirva.

When to take Xanirva
Tablets should be taken every day until the doctor decides to stop treatment. It is best to take the tablet(s) at the same time each day, as this makes it easier to remember.
The doctor will decide how long the patient should continue treatment.
Prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If heart rhythm needs to be restored to normal through a cardioversion procedure, Xanirva should be taken as directed by the doctor.

Taking more Xanirva than prescribed
If a patient takes more Xanirva than prescribed, contact a doctor immediately. Taking too high a dose of Xanirva increases the risk of bleeding.

Missed dose
Adults, children and adolescents:

If the patient takes one 20 mg tablet or one 15 mg tablet once daily and a dose is missed, take the tablet as soon as possible. Do not take more than one tablet in a single day to make up for the missed dose. Take the next tablet the following day, then continue taking one tablet once daily.

Adults:

If the patient takes one 15 mg tablet twice daily and a dose is missed, take the tablet as soon as possible. Do not take more than two 15 mg tablets in a single day. If the patient forgets to take a dose, they may take two 15 mg tablets together to ensure a total of two tablets (30 mg) are taken within one day. The next day, resume taking one 15 mg tablet twice daily.

Stopping Xanirva treatment
Do not stop taking Xanirva without first consulting your doctor, as Xanirva treats and prevents serious medical conditions.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.
Like other medicines with a similar mechanism of action (reducing blood clot formation), Xanirva may cause bleeding, which could potentially be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious or visible.
You should contact a doctor immediately if any of the following adverse reactions occur in the patient or child:

Signs of bleeding:

Bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, decreased level of consciousness, and neck stiffness. A serious medical emergency. Seek immediate medical help!),
Prolonged or heavy bleeding, unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. The doctor may decide that close monitoring of the patient or a change in treatment is necessary.

Signs of severe skin reactions:

Widespread, acute skin rash, blistering, or mucosal lesions, e.g., on the tongue or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
Drug reaction with eosinophilia and systemic symptoms (DRESS), characterized by rash, fever, internal organ inflammation, hematological abnormalities, and systemic involvement. These adverse reactions are very rare (may occur in less than 1 in 10,000 people).

Signs of serious allergic reaction:

Swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing; urticaria and breathing difficulties; sudden drop in blood pressure. The frequency of severe hypersensitivity reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in less than 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible adverse reactions in adults, children, and adolescents:
Common (may occur in 1 in 10 people)

Decreased number of red blood cells, which may cause paleness of the skin and lead to weakness or shortness of breath
Gastrointestinal or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding
Bleeding into the eye (including bleeding from the sclera of the eye)
Bleeding into tissues or body cavities (hematoma, bruising)
Presence of blood in sputum during coughing (hemoptysis)
Bleeding from the skin or subcutaneous bleeding
Bleeding after surgery
Oozing of blood or fluid from a surgical wound
Limb swelling
Limb pain
Kidney function disorders (may be observed in tests performed by a doctor)
Fever
Stomach pain, indigestion, nausea or vomiting, constipation, diarrhea
Low blood pressure (symptoms may include dizziness or fainting upon standing)
Generalized weakness and fatigue, headache, dizziness
Rash, itching of the skin
Increased activity of certain liver enzymes, which may be evident in blood test results.

Uncommon (may occur in 1 in 100 people)

Bleeding into the brain or inside the skull (see above signs of bleeding),
Bleeding into a joint causing pain and swelling
Thrombocytopenia (low number of platelets, blood cells involved in blood clotting)
Allergic reactions, including allergic skin reactions
Liver function disorders (may be observed in tests performed by a doctor)
Blood tests may show increased bilirubin levels, increased activity of certain pancreatic or liver enzymes, or increased platelet count
Fainting
Malaise
Rapid heartbeat
Dry mouth
Urticaria

Rare (may occur in 1 in 1,000 people)

Bleeding into muscles
Cholestasis (bile stasis), hepatitis including liver cell damage
Yellowing of the skin and eyes (jaundice)
Localized swelling
Blood collection (hematoma) in the groin as a complication of cardiac catheterization when the catheter is inserted into an artery in the leg (pseudoaneurysm)

Very rare (may occur in 1 in 10,000 people)

Eosinophilia, an accumulation of a type of white granulocytic blood cells causing lung inflammation (eosinophilic pneumonia).

Frequency unknown (cannot be estimated from available data)

Kidney failure following severe bleeding
Bleeding in the kidneys, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy)
Increased pressure in the muscles of arms and legs following bleeding, which may cause pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome following bleeding).

Adverse reactions in children and adolescents
In general, adverse reactions observed in children and adolescents treated with rivaroxaban were similar in type to those observed in adults and were mostly mild to moderate in severity.
Adverse reactions observed more frequently in children and adolescents:
Very common (may occur in more than 1 in 10 people)

Headache
Fever
Nosebleeds
Vomiting

Common (may occur in 1 in 10 people)

Rapid heartbeat
Blood tests may show increased bilirubin levels (a bile pigment)
Thrombocytopenia (low number of platelets, blood cells that help in blood clotting)
Heavy menstrual bleeding

Uncommon (may occur in 1 in 100 people)

Blood tests may show increased levels of a subcategory of bilirubin (direct bilirubin, a bile pigment).

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, consult a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps gather more information on the safety of the medicine. Adverse reactions can also be reported to the marketing authorization holder or its representative in Poland.

5. How to store Xanirva

Keep this medicine out of sight and reach of children.
No special storage instructions are required for this medicine.
Do not use this medicine after the expiry date stated on the outer carton and blister marked EXP. The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Xanirva contains

The active substance is rivaroxaban. One coated tablet contains 15 mg or 20 mg of rivaroxaban.
Other ingredients are: tablet core: monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose 2910, sodium lauryl sulfate, magnesium stearate. coating: hypromellose 2910, titanium dioxide (E 171), macrogol, iron oxide, red (E 172).

What Xanirva looks like and contents of the pack
Xanirva 15 mg: red, round, biconvex coated tablets with a diameter of approximately 9.5 mm, embossed with the marking "15" on one side, smooth on the other.
Xanirva 15 mg is available in packs containing 10, 14, 28, 30, 42, 50, 98 and 100 coated tablets.
Xanirva 20 mg: red-brown, round, biconvex coated tablets with a diameter of approximately 10.5 mm, embossed with the marking "20" on one side, smooth on the other.
Xanirva 20 mg is available in packs containing 10, 14, 28, 30, 50, 98 and 100 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130, Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer / Importer
S.C. Zentiva S.A.
B-dul Theodor Pallady nr. 50, Sector 3
Bucharest 032266, Romania
Pharmadox Healthcare Ltd
KW20A Kordin Industrial Park, Paola
PLA3000 Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Czech Republic, Bulgaria, Estonia, Lithuania, Latvia, Poland, Romania, Slovakia, United Kingdom, Greece: Xanirva

For further information about this medicinal product, please contact:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. (22) 375 92 00